Health Condition 1: K00-K95- Diseases of the digestive system
Conditions
Interventions
Intervention1: Vedolizumab (T): Dosage Level: 300 mg at zero, two and six weeks and then every eight weeks after that till Week 22, Route of Administration: Intravenous infusion
Control Intervention1:
Sponsors
Intas Pharmaceuticals Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1 Participant must sign an ICF indicating that the participant understands the purpose of, and procedures required for the study as described in section 10.1.3 and in this protocol and is willing to participate in the study. 2 Male or female participants with 18 completed years of age or older at the time of signing the informed consent. 3 Participants must have a documented diagnosis of UC at least three months duration before screening, confirmed by:Medical records with a report of an endoscopy, which shows features consistent with UC, as determined by the procedure performing physician, AND Medical record documentation of a histopathology report showing features consistent with UC, as determined by the local pathologist. Note: If a histopathology report is unavailable, histologic samples can be obtained at the screening endoscopy and sent to a local laboratory to confirm UC diagnosis before randomization. The screening endoscopy must show features consistent with UC, and medical records must still document a clinical diagnosis of UC at least three months duration before screening. 4 Participant has moderately to severely active UC as defined by a Complete Mayo score of 6 to 12 (both inclusive) with an endoscopic subscore (ES) greater than or equal to 2 (with endoscopy performed within ten days before the first dose of investigational intervention), a rectal bleeding subscore greater than or equal to 1, and a stool frequency subscore greater than or equal to 1 during the screening period (before randomization on Day 1). 5 Participants have evidence of UC extending proximal to the rectosigmoid junction (greater than or equal to 15 cm of the involved colon from the anal margin) as determined by screening endoscopy. Participants with rectal sparing on screening endoscopy must have documentation of rectal involvement on a prior endoscopy and histopathology report to confirm UC diagnosis. 6 Have documentation of:A surveillance colonoscopy for dysplasia (performed according to local standards) within 12 months before the first administration of investigational intervention for: a participants with pancolitis of greater than 8 years duration or a participants with left-sided colitis of greater than 12 years of duration or a participants with primary sclerosing cholangitis. OR Participants with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age greater than 50 years, or other known risk factors must either have had a full colonoscopy to assess for the presence of adenomatous polyps within five years before the first administration of investigational intervention. Participants who do not have a colonoscopy report available in source documentation must have a colonoscopy at screening. 7 Participants must have an inadequate response to, loss of response to, or intolerance to a treatment course of one or more of the following standard of care medications described below as A OR B. Documentation of dose, dates, frequency, route of administration, and duration of the prior failed treatment, as well as documents that the participant had persistent disease activity UC treatment, is required. Signs and symptoms of persistently active disease for this inclusion criteria are defined as the lack of improvement or worsening of at least 1 of the following: stool frequency, rectal bleeding, daily abdominal pain, worsening in urgency, and endoscopic appearance of
Exclusion criteria
Exclusion criteria: 1 Documented medical history of uncontrolled, clinically significant intercurrent cardiac, vascular, pulmonary, gastrointestinal other than ulcerative colitis, endocrine, neurologic, haematologic, rheumatologic, psychiatric, or metabolic disturbances or any other medical condition(s) for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments. 2 Known history of serious or severe allergies, hypersensitivity, or intolerance to any chimeric, human, or humanized antibodies, fusion proteins, or murine proteins OR to investigational interventions, components/ excipients thereof (L-histidine, L-histidine monohydrochloride, L-arginine hydrochloride, Sucrose, Polysorbate 80), OR any other drug allergy that, in the opinion of the investigator, contraindicates participation in the study. 3 Contraindications to the use of any of the investigational interventions or components/excipients per DCGI approved PI of Kynteles[3] or SmPC of Entyvio [1] 4 Participant has one or more of the following gastrointestinal conditions with documented evidence at the screening visit a. Have a current diagnosis of Crohn s disease or inflammatory bowel disease unclassified (IBD-U) (formerly known as indeterminate colitis), ischemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis or any other abnormality which may affect the objective assessment as per PI s judgment b. Presence of symptomatic colonic or small bowel obstruction, confirmed by objective radiographic or endoscopic evidence of stricture with resulting obstruction (dilation of the colon or small bowel proximal to the stricture on barium radiograph or an inability to traverse the stricture at endoscopy). c. Previous bowel resection or intestinal or intra-abdominal surgery. d. Presence of a stoma. e. Presence or history of a fistula. f. Current or recent (within 12 weeks before the randomization visit) evidence of fulminant colitis, abdominal abscess, toxic megacolon, or bowel perforation. g. Any history or current evidence of cancer of the gastrointestinal tract. 5 Has prior or current evidence of definite low-grade or high-grade colonic dysplasia including dysplasia identified during the screening endoscopy that has not been completely removed. Once completely removed, the participant is eligible for the study. 6 Has severe extensive colitis as evidenced by: 7 Exclusion Criteria Related to Prior or Concomitant Therapy 8 Participants with ongoing/inadequately treated serious, opportunistic or chronic/recurring extraintestinal infections at screening visit including but not limited to the following. 9 Any current signs or symptoms of active extraintestinal infection within two weeks before the first dose of study intervention, except for the following: 10 Have evidence of active infectious herpes zoster infection less than or equal to 8 weeks before screening. Herpes zoster infections remain active until all vesicles are crusted over. 11 Had evidence of treatment for Clostridium difficile within 4 weeks of the first dose of investigational intervention or test positive for C. difficile. If a participant is positive for C. difficile at screening, the participant may be treated and rescreen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To establish non-inferiority for the clinical response rates associated with vedolizumab-test compared to vedolizumab-reference at Week 6 in participants with moderately to severely active ulcerative colitisTimepoint: Week 0, Week 2, Week 6, Week 14, Week 22 and Week 26 / EOS visit | — |
Secondary
| Measure | Time frame |
|---|---|
| To further evaluate the efficacy of vedolizumab-test compared to vedolizumab-reference in participants with moderately to severely active ulcerative colitisTimepoint: Week 0, Week 2, Week 6, Week 14, Week 22 and Week 26 / EOS visit | — |
Countries
India
Contacts
Public ContactDr Jogesh Mahajan
Lambda Therapeutic Research Ltd
Outcome results
None listed